Depression in youths is a prevalent, recurrent, and frequently chronic disorder that is associated with significant social and academic impairment, as well as considerable public health burden.1,10 Parental depression is associated with increased risk for the development of youth depression, with intergenerational transmission facilitated by both genetic and environmental factors.3,4 One psychosocial model of how parental depression leads to youth depression is through impaired parenting and parent-youth interactions.5,6 While past work on the intergenerational transmission of depression has tended to focus on types of impoverished parenting behaviors, variability in those behaviors has been more frequently overlooked. However, previous research suggests that the regularity of social interactions can entrain biological rhythms relevant to depression. The proposed project seeks to examine whether disruptions to the consistency and timing of parent-youth interactions contribute to the intergenerational transmission of depression via effects on neuroendocrine and inflammatory processes. Using data from two longitudinal studies, the present work will first explore whether parental depressive symptoms are related to disruptions in the regularity of parent-youth interactions. Through regression analyses and multilevel linear modeling (MLM), associations will next be explored between the regularity of these parent-youth interactions and youth's cortisol rhythms, depression- relevant cytokine activity, and emotion regulation abilities, [with exploratory analyses examining expression of two genes]. Lastly, structural equation modeling (SEM) will be employed to test whether regularity of parent- youth interactions mediates the proposed association between parental depressive symptoms and youth's inflammatory, neuroendocrine, and emotion regulation processes, with exploratory analyses examining longitudinal links to youth depressive symptoms. Training activities include: 1) extensive hands-on training in wet-lab procedures for measuring inflammatory processes [and gene expression in blood samples,] 2) completion of additional coursework in statistics (e.g., MLM), developmental psychobiology, and immunology, and 3) participation in summer workshops on statistics (e.g., SEM) and biomarker research. These experiences will provide a strong foundation both for the completion of the proposed project and for developing a future independent program of research on psychobiological factors associated with the intergenerational transmission of depression. Consistent with many of the objectives outlined in the NIMH Strategic Plan, 55 the proposed project has the potential to make a contribution to the research literature by identifying family-related psychobiological mechanisms relevant to the intergenerational transmission of depression. These findings may also have implications for the clinical treatment of depression in parents and youth by highlighting structural dimensions of the family environment that may be particularly amenable to change.